Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-51255
PROVIDER: PRJNA222226 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
2013-11-24 | GSE51255 | GEO
Project description:The miR-126/VEGFR2 axis controls the innate response to pathogen-associated nucleic acids
2015-07-27 | E-GEOD-51255 | ExpressionAtlas
Project description:microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs. Plasmactyoid dendritic cells were FACS-sorted from spleens from wildtype and miR-126 KO mice and their RNA extracted. RNA was amplified, labeled and hybridized to Mouse Gene 1.0 ST arrays with the data generation and quality control pipeline of 19 the Immunological Genome Project (www.immgen.org). Raw data were background-corrected and normalized using the RMA algorithm.
2013-11-24 | E-GEOD-51255 | biostudies-arrayexpress
Project description:Hypoxia controls reparative angiogenesis. MiRNAs are master regulators of gene expression in hypoxia and angiogenesis. However, we do not yet have a clear understanding of how hypoxia-induced miRNAs modulate vasoreparative processes. Here, we identify miR-130a as a mediator of the hypoxic response in human primary endothelial colony forming cells (ECFCs), a well-characterized subtype of endothelial progenitor. Under hypoxic conditions, miR-130a overexpression enhances ECFC pro-angiogenic capacity in vitro and potentiates their vasoreparative properties in vivo. Mechanistically, miR-130a orchestrates upregulation of VEGFR2, activation of STAT3-dependent transcription, and accumulation of HIF1α via translational inhibition of DDX6. These findings unveil a new role for miR-130a in hypoxia, whereby it modulates the VEGFR2/STAT3/HIF1α axis to increase the vasoregenerative capacity of ECFCs.
2022-12-06 | GSE142123 | GEO
Project description:Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) is accumulated during pathogen infection or pathogenesis, it remains unclear whether and how intracellular ssDNA stimulates the immune system. We report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif-dependent manner. Through a genome-wide CRISPRLCas9 screen, we identified Schlafen-11 (SLFN11), which is essential for the response to endogenous and pathogen ssDNA. SLFN11 directly binds ssDNA containing CGT motifs and translocates to the cytoplasm upon ssDNA recognition. The mice deficient in SLFN9, the homologue of SLFN11, were resistant to CGT ssDNA-induced inflammation, acute hepatitis and septic shock. This study establishes CGT ssDNA and SLFN11/9 as a novel type of immunostimulatory nucleic acids and pattern recognition receptors, respectively.
2024-05-07 | GSE266887 | GEO
Project description:Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduced AML rate and extended survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibited AML cell survival, reduced leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. Combination of miRisten with chemotherapy further enhanced the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a new therapeutic approach for inv(16) AML.
2021-09-15 | GSE184015 | GEO
Project description:Toll-like receptors (TLRs) are mediators in the innate immune response by recognizing nucleic acids derived from microbial components as for TLR9 binding ability for CpG rich bacterial DNA. We studied the differential expression by microarrays of all known T-UCRs and near genes in a series of 6 primary B-CLL cases cells comparing cells treated in vitro with CpG ODN versus mock controls.
2018-12-31 | GSE57160 | GEO
Project description:The interactions between proteins and nucleic acids have a fundamental function in many biological processes well beyond nuclear gene transcription and include RNA homeostasis, protein translation and pathogen sensing for innate immunity. While our knowledge of the ensemble of proteins binding individual mRNAs in mammalian cells has greatly been augmented by recent surveys, no systematic study on the native proteins of human cells differentially engaging various types of nucleic acids in a non sequence-specific manner has been reported. We designed an experimental approach to cover the non sequence-specific RNA and DNA binding space broadly, including methylation, and test for its ability to interact with the human proteome. We used 25 rationally designed nucleic acid probes in an affinity purification mass spectrometry and bioinformatics workflow to identify proteins from whole cell extracts of three different human cell lines. The proteins were profiled for their binding preferences to the different general types of nucleic acids. The study identified 746 high confidence direct binders, 249 of which were devoid of previous experimental evidence for binding nucleic acids. We could assign 513 specific affinities for sub-types of nucleic acid probes to 219 distinct proteins and to individual domains. The evolutionary conserved protein YB-1, previously associated with cancer and gene regulation, is shown to bind methylated cytosine preferentially conferring YB-1 a potential epigenetic function. Collectively, the dataset represents a rich resource of experimentally determined nucleic acid-specific binding proteins in humans and, indirectly, for other species. Identification of genomic YB-1 binding sites in HEK293 cells
2013-06-18 | E-GEOD-47539 | biostudies-arrayexpress
Project description:Cutaneous lupus erythematosus (CLE) is a photosensitive autoimmune disease characterized by a strong type-I-interferon (IFN) associated inflammation. Keratinocytes are known to determine the interface-dermatitis-pattern in CLE by production of proinflammatory cytokines in the lower epidermis. These cytokines drive a cytotoxic anti-epithelial immune response resulting in keratinocytic cell death and release of endogenous nucleic acids (eNA). We hypothesized that these eNA (RNA- and DNA-motifs) have the capacity to activate innate immune pathways in keratinocytes via pathogen-recognition-receptors (PRR). Gene expression analyses revealed an excessive activation of innate immune response pathways with strong expression of IFN-regulated cytokines in CLE skin lesions. Cultured keratinocytes produce large amounts of these cytokines in response to stimulation of PRR with eNA. UV-stimulation enhances the immunogenicity of eNA and induces CLE-like skin lesions in knockout mice lacking the cytosolic DNase TREX1. Our results provide evidence for a pathogenetic role of endogenous nucleic acids in CLE. They are released within the cytotoxic inflammation along the dermo-epidermal junction and have the capacity to drive the LE-typical inflammation. UV-irradiation supports this inflammation by generation of highly immunostimulatory DNA motifs (8-OHG). These findings explain the photosensitivity of lupus patients and identify pathways of the innate immune system as targets for future therapies.
2017-03-01 | GSE95474 | GEO
Project description:The interactions between proteins and nucleic acids have a fundamental function in many biological processes well beyond nuclear gene transcription and include RNA homeostasis, protein translation and pathogen sensing for innate immunity. While our knowledge of the ensemble of proteins binding individual mRNAs in mammalian cells has greatly been augmented by recent surveys, no systematic study on the native proteins of human cells differentially engaging various types of nucleic acids in a non sequence-specific manner has been reported. We designed an experimental approach to cover the non sequence-specific RNA and DNA binding space broadly, including methylation, and test for its ability to interact with the human proteome. We used 25 rationally designed nucleic acid probes in an affinity purification mass spectrometry and bioinformatics workflow to identify proteins from whole cell extracts of three different human cell lines. The proteins were profiled for their binding preferences to the different general types of nucleic acids. The study identified 746 high confidence direct binders, 249 of which were devoid of previous experimental evidence for binding nucleic acids. We could assign 513 specific affinities for sub-types of nucleic acid probes to 219 distinct proteins and to individual domains. The evolutionary conserved protein YB-1, previously associated with cancer and gene regulation, is shown to bind methylated cytosine preferentially conferring YB-1 a potential epigenetic function. Collectively, the dataset represents a rich resource of experimentally determined nucleic acid-specific binding proteins in humans and, indirectly, for other species.
2013-06-18 | GSE47539 | GEO